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Fundamentals of
Tuberculosis (TB)
name : Avinash k
1
TB in the United States
• From 1953 to 1984, reported cases
decreased by approximately 5.6% each
year
• From 1985 to 1992, reported cases
increased by 20%
• 25,313 cases reported in 1993
• Since 1993, cases are steadily declining
2
Factors Contributing to the
Increase in TB Cases
• HIV epidemic
• Increased immigration from high-
prevalence countries
• Transmission of TB in congregate settings
(e.g., correctional facilities, long term care)
• Deterioration of the public health care
infrastructure
3
Transmission and
Pathogenesis of TB
• Caused by Mycobacterium tuberculosis (M.
tuberculosis)
• Spread person to person through airborne particles
that contain M. tuberculosis, called droplet nuclei
• Transmission occurs when an infectious person
coughs, sneezes, laughs, or sings
• Prolonged contact needed for transmission
• 10% of infected persons will develop TB disease at
some point in their lives
4
Sites of TB Disease
• Pulmonary TB occurs in the lungs
– 85% of all TB cases are pulmonary
• Extrapulmonary TB occurs in places other than the
lungs, including the:
– Larynx
– Lymph nodes
– Brain and spine
– Kidneys
– Bones and joints
• Miliary TB occurs when tubercle bacilli enter the
bloodstream and are carried to all parts of the body
5
Not Everyone Exposed
Becomes Infected
• Probability of transmission depends
on:
– Infectiousness
– Type of environment
– Length of exposure
• 10% of infected persons will develop
TB disease at some point in their lives
– 5% within 1-2 years
– 5% at some point in their lives
6
Persons at Risk for Developing
TB Disease
• Persons at high risk for developing TB
disease fall into 2 categories
– Those who have been recently infected
– Those with clinical conditions that increase
their risk of progressing from LTBI to TB
disease
7
Recent Infection as a
Risk Factor
Persons more likely to have been recently
infected include
• Close contacts to persons with infectious TB
• Skin test converters (within past 2 years)
• Recent immigrants from TB-endemic areas
(within 5 years of arrival to the U.S.)
• Children ≤ 5 years with a positive TST
• Residents and employees of high-risk
congregate settings (e.g. correctional facilities,
homeless shelters, healthcare facilities)
8
Increased Risk for Progression to
TB Disease
Persons more likely to progress from LTBI to TB
disease include
• HIV infected persons
• Those with history of prior, untreated TB
• Underweight or malnourished persons
• Injection drug use
• Those receiving TNF-α antagonists for treatment
of rheumatoid arthritis or Crohn’s disease
• Certain medical conditions
9
Latent TB Infection (LTBI)
• Occurs when person breathes in bacteria
and it reaches the air sacs (alveoli) of lung
• Immune system keeps bacilli contained
and under control
• Person is not infectious and has no
symptoms
10
TB Disease
• Occurs when immune system cannot
keep bacilli contained
• Bacilli begin to multiply rapidly
• Person develops TB symptoms
11
LTBI vs. TB Disease
LTBI TB Disease
Tubercle bacilli in the body
TST or QFT-Gold® result usually positive
Chest x-ray usually normal Chest x-ray usually abnormal
Sputum smears and cultures
negative
Symptoms smears and cultures
positive
No symptoms Symptoms such as cough, fever,
weight, loss
Not infectious Often infectious before treatment
Not a case of TB A case of TB
12
Targeted Testing
• Detects persons with LTBI who would
benefit from treatment
• De-emphasize testing of groups of people
who are not at risk (mass screening)
• Consider using a risk assessment tool
• Testing should be done only if there is an
intent to treat
• Can help reduce the waste of resources
and prevent unnecessary treatment
13
Groups to Target with the
Tuberculin Skin Test
• Persons with or at risk for HIV infection
• Close contacts of persons with infectious TB
• Persons with certain medical conditions
• Injection drug users
• Foreign-born persons from areas where TB is common
• Medically underserved, low-income populations
• Residents of high-risk congregate settings
• Locally identified high-prevalence groups
14
Administering the TST
• Use Mantoux tuberculin skin test
• 0.1 mL of 5-TU of purified protein derivative
(PPD) solution injected intradermally
• Use a 27 gauge needle
• Produce a wheal that is 6-10mm in
diameter
15
Reading the TST
• Read within 48-72 hours
• Measure induration, not erythema
• Positive reactions can be measured
accurately for up to 7 days
• Negative reactions can be read
accurately for only 72 hours
16
TST Interpretation - 1
5 mm of induration is positive in:
– HIV-infected persons
– Close contacts to an infectious TB case
– Persons who have chest x-ray findings
consistent with prior untreated TB
– Organ transplant recipients
– Persons who are immunosuppressed (e.g.,
those taking the equivalent of >15 mg/d of
prednisone for 1 month or those taking TNF-α
antagonists)
17
TST Interpretation - 2
10 mm induration is positive in:
– Recent immigrants (within last 5 years) from a
high-prevalence country
– Injection drug users
– Persons with other high-risk medical conditions
– Residents or employees of high-risk congregate
settings
– Mycobacteriology laboratory personnel
– Children < 4 years of age; infants, children, and
adolescents exposed to adults at high risk
18
TST Interpretation - 3
15 mm induration is positive in:
• Persons with no known risk factors for
TB
19
Recording TST Results
• Record results in millimeters of induration,
not “negative” or “positive”
• Only trained healthcare professionals
should read and interpret TST results
20
False Positive TST Reactions
• Nontuberculous mycobacteria
– Reactions are usually ≤10mm of induration
• BCG vaccination
– Reactivity in BCG vaccine recipients generally wanes
over time
– Positive TST results is likely due to TB infection if risk
factors are present
– BCG-vaccinated persons with positive TST result
should be evaluated for treatment of LTBI
– QFT is able to distinguish M.tb from other
mycobacteria and BCG vaccine
21
False Negative TST Reactions
• Anergy, or inability to react to TST
because of weakened immune system
• Recent TB infection (2-10 weeks after
exposure)
• Very young age (newborns)
• Recent live-virus vaccination can
temporarily suppress TST reactivity
• Poor TST administration technique (too
shallow or too deep, or wheal is too small)
22
Boosting
• Some people with history of LTBI lose their
ability to react to tuberculin (immune
system “forgets” how to react to TB-like
substance, i.e., PPD)
• Initial TST may stimulate (boost) the ability
to react to tuberculin
• Positive reactions to subsequent tests may
be misinterpreted as new infections rather
than “boosted” reactions
23
Two-Step Testing - 1
• A strategy for differentiating between
boosted reactions and reactions caused
by recent TB infection
• Use two-step testing for initial (baseline)
skin testing of adults who will be re-tested
periodically
• 2nd skin test given 1-3 weeks after
baseline
24
Two-Step Testing - 2
• If the 1st TST is positive, consider the
person infected
• If the 1st TST is negative, administer 2nd
TST in 1-3 weeks
• If the 2nd TST is positive, consider the
person infected
• If the 2nd TST is negative, consider the
person uninfected at baseline
25
Infectiousness - 1
• Patients should be considered infectious if they:
– Are undergoing cough-inducing procedures
– Have sputum smears positive for acid-fast bacilli
(AFB) and:
• Are not receiving treatment
• Have just started treatment, or
• Have a poor clinical or bacterial response to
treatment
– Have cavitary disease
• Extrapulmonary TB patients are not infectious
26
Infectiousness - 2
• Patients are not considered infectious if
they meet all these criteria:
– Received adequate treatment for 2-3 weeks
– Favorable clinical response to treatment
– 3 consecutive negative sputum smears results
from sputum collected on different days
27
Techniques to Decrease TB
Transmission
• Instruct patient to:
– Cover mouth when coughing or sneezing
– Wear mask as instructed
– Open windows to assure proper ventilation
– Do not go to work or school until instructed by
physician
– Avoid public places
– Limit visitors
– Maintain home or hospital isolation as ordered
28
Evaluation for TB
• Medical history
• Physical examination
• Mantoux tuberculin skin test
• Chest x-ray
• Bacteriologic exam (smear and culture)
29
Symptoms of TB
• Productive prolonged cough*
• Chest pain*
• Hemoptysis*
• Fever and chills
• Night sweats
• Fatigue
• Loss of appetite
• Weight loss
*Commonly seen in cases of pulmonary TB
30
Chest x-Ray
• Obtain chest x-ray for patients with
positive TST results or with symptoms
suggestive of TB
• Abnormal chest x-ray, by itself, cannot
confirm the diagnosis of TB but can be
used in conjunction with other diagnostic
indicators
31
Sputum Collection
• Sputum specimens are essential to
confirm TB
– Specimens should be from lung secretions,
not saliva
• Collect 3 specimens on 3 different days
• Spontaneous morning sputum more
desirable than induced specimens
• Collect sputum before treatment is
initiated
32
Smear Examination
• Strongly consider TB in patients with
smears containing acid-fast bacilli (AFB)
• Use subsequent smear examinations to
assess patient’s infectiousness and
response to treatment
33
Culture
• Used to confirm diagnosis of TB
• Culture all specimens, even if smear
is negative
• Initial drug isolate should be used to
determine drug susceptibility
34
Treatment of Latent TB Infection
• Daily Isoniazid therapy for 9 months
– Monitor patients for signs and symptoms of
hepatitis and peripheral neuropathy
• Alternate regimen – Rifampin for 4 months
35
Treatment of TB Disease
• Include four 1st-line drugs in initial regimen
– Isoniazid (INH)
– Rifampin (RIF)
– Pyrazinamide (PZA)
– Ethambutol (EMB)
• Adjust regimen when drug susceptibility
results become available or if patient has
difficulty with any of the medications
• Never add a single drug to a failing regimen
• Promote adherence and ensure treatment
completion
36
Directly Observed Therapy (DOT)
• Health care worker watches patient
swallow each dose of medication
• DOT is the best way to ensure adherence
• Should be used with all intermittent
regimens
• Reduces relapse of TB disease and
acquired drug resistance
37
Clinical Monitoring
Instruct patients taking TB medications to
immediately report the following:
– Rash
– Nausea, loss of appetite, vomiting, abdominal
pain
– Persistently dark urine
– Fatigue or weakness
– Persistent numbness in hands or feet
38
Drug Resistance
• Primary - infection with a strain of M.
tuberculosis that is already resistant to one
or more drugs
• Acquired - infection with a strain of M.
tuberculosis that becomes drug resistant
due to inappropriate or inadequate
treatment
39
Barriers to Adherence
• Stigma
• Extensive duration of treatment
• Adverse reactions to medications
• Concerns of toxicity
• Lack of knowledge about TB and its
treatment
40
Improving Adherence
• Adherence is the responsibility of the
provider, not the patient and can be
ensured by:
– Patient education
– Directly observed therapy (DOT)
– Case management
– Incentives/enablers
41
Measures to Promote Adherence
• Develop an individualized treatment plan for
each patient
• Provide culturally and linguistically
appropriate care to patient
• Educate patient about TB, medication dosage,
and possible adverse reactions
• Use incentives and enablers to address
barriers
• Facilitate access to health and social services
42
Completion of Therapy
• Based on total number of doses
administered, not duration of treatment
• Extend or re-start if there were frequent or
prolonged interruptions
43
Meeting the Challenge
• Prevent TB by assessing risk factors
• If risk is present, perform TST
• If TST is positive, rule out active disease
• If active disease is ruled out, initiate
treatment for LTBI
• If treatment is initiated, ensure completion
44
Remember
“A decision to test is a decision to treat.”
45

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FundamentalsofTB.pdf

  • 2. TB in the United States • From 1953 to 1984, reported cases decreased by approximately 5.6% each year • From 1985 to 1992, reported cases increased by 20% • 25,313 cases reported in 1993 • Since 1993, cases are steadily declining 2
  • 3. Factors Contributing to the Increase in TB Cases • HIV epidemic • Increased immigration from high- prevalence countries • Transmission of TB in congregate settings (e.g., correctional facilities, long term care) • Deterioration of the public health care infrastructure 3
  • 4. Transmission and Pathogenesis of TB • Caused by Mycobacterium tuberculosis (M. tuberculosis) • Spread person to person through airborne particles that contain M. tuberculosis, called droplet nuclei • Transmission occurs when an infectious person coughs, sneezes, laughs, or sings • Prolonged contact needed for transmission • 10% of infected persons will develop TB disease at some point in their lives 4
  • 5. Sites of TB Disease • Pulmonary TB occurs in the lungs – 85% of all TB cases are pulmonary • Extrapulmonary TB occurs in places other than the lungs, including the: – Larynx – Lymph nodes – Brain and spine – Kidneys – Bones and joints • Miliary TB occurs when tubercle bacilli enter the bloodstream and are carried to all parts of the body 5
  • 6. Not Everyone Exposed Becomes Infected • Probability of transmission depends on: – Infectiousness – Type of environment – Length of exposure • 10% of infected persons will develop TB disease at some point in their lives – 5% within 1-2 years – 5% at some point in their lives 6
  • 7. Persons at Risk for Developing TB Disease • Persons at high risk for developing TB disease fall into 2 categories – Those who have been recently infected – Those with clinical conditions that increase their risk of progressing from LTBI to TB disease 7
  • 8. Recent Infection as a Risk Factor Persons more likely to have been recently infected include • Close contacts to persons with infectious TB • Skin test converters (within past 2 years) • Recent immigrants from TB-endemic areas (within 5 years of arrival to the U.S.) • Children ≤ 5 years with a positive TST • Residents and employees of high-risk congregate settings (e.g. correctional facilities, homeless shelters, healthcare facilities) 8
  • 9. Increased Risk for Progression to TB Disease Persons more likely to progress from LTBI to TB disease include • HIV infected persons • Those with history of prior, untreated TB • Underweight or malnourished persons • Injection drug use • Those receiving TNF-α antagonists for treatment of rheumatoid arthritis or Crohn’s disease • Certain medical conditions 9
  • 10. Latent TB Infection (LTBI) • Occurs when person breathes in bacteria and it reaches the air sacs (alveoli) of lung • Immune system keeps bacilli contained and under control • Person is not infectious and has no symptoms 10
  • 11. TB Disease • Occurs when immune system cannot keep bacilli contained • Bacilli begin to multiply rapidly • Person develops TB symptoms 11
  • 12. LTBI vs. TB Disease LTBI TB Disease Tubercle bacilli in the body TST or QFT-Gold® result usually positive Chest x-ray usually normal Chest x-ray usually abnormal Sputum smears and cultures negative Symptoms smears and cultures positive No symptoms Symptoms such as cough, fever, weight, loss Not infectious Often infectious before treatment Not a case of TB A case of TB 12
  • 13. Targeted Testing • Detects persons with LTBI who would benefit from treatment • De-emphasize testing of groups of people who are not at risk (mass screening) • Consider using a risk assessment tool • Testing should be done only if there is an intent to treat • Can help reduce the waste of resources and prevent unnecessary treatment 13
  • 14. Groups to Target with the Tuberculin Skin Test • Persons with or at risk for HIV infection • Close contacts of persons with infectious TB • Persons with certain medical conditions • Injection drug users • Foreign-born persons from areas where TB is common • Medically underserved, low-income populations • Residents of high-risk congregate settings • Locally identified high-prevalence groups 14
  • 15. Administering the TST • Use Mantoux tuberculin skin test • 0.1 mL of 5-TU of purified protein derivative (PPD) solution injected intradermally • Use a 27 gauge needle • Produce a wheal that is 6-10mm in diameter 15
  • 16. Reading the TST • Read within 48-72 hours • Measure induration, not erythema • Positive reactions can be measured accurately for up to 7 days • Negative reactions can be read accurately for only 72 hours 16
  • 17. TST Interpretation - 1 5 mm of induration is positive in: – HIV-infected persons – Close contacts to an infectious TB case – Persons who have chest x-ray findings consistent with prior untreated TB – Organ transplant recipients – Persons who are immunosuppressed (e.g., those taking the equivalent of >15 mg/d of prednisone for 1 month or those taking TNF-α antagonists) 17
  • 18. TST Interpretation - 2 10 mm induration is positive in: – Recent immigrants (within last 5 years) from a high-prevalence country – Injection drug users – Persons with other high-risk medical conditions – Residents or employees of high-risk congregate settings – Mycobacteriology laboratory personnel – Children < 4 years of age; infants, children, and adolescents exposed to adults at high risk 18
  • 19. TST Interpretation - 3 15 mm induration is positive in: • Persons with no known risk factors for TB 19
  • 20. Recording TST Results • Record results in millimeters of induration, not “negative” or “positive” • Only trained healthcare professionals should read and interpret TST results 20
  • 21. False Positive TST Reactions • Nontuberculous mycobacteria – Reactions are usually ≤10mm of induration • BCG vaccination – Reactivity in BCG vaccine recipients generally wanes over time – Positive TST results is likely due to TB infection if risk factors are present – BCG-vaccinated persons with positive TST result should be evaluated for treatment of LTBI – QFT is able to distinguish M.tb from other mycobacteria and BCG vaccine 21
  • 22. False Negative TST Reactions • Anergy, or inability to react to TST because of weakened immune system • Recent TB infection (2-10 weeks after exposure) • Very young age (newborns) • Recent live-virus vaccination can temporarily suppress TST reactivity • Poor TST administration technique (too shallow or too deep, or wheal is too small) 22
  • 23. Boosting • Some people with history of LTBI lose their ability to react to tuberculin (immune system “forgets” how to react to TB-like substance, i.e., PPD) • Initial TST may stimulate (boost) the ability to react to tuberculin • Positive reactions to subsequent tests may be misinterpreted as new infections rather than “boosted” reactions 23
  • 24. Two-Step Testing - 1 • A strategy for differentiating between boosted reactions and reactions caused by recent TB infection • Use two-step testing for initial (baseline) skin testing of adults who will be re-tested periodically • 2nd skin test given 1-3 weeks after baseline 24
  • 25. Two-Step Testing - 2 • If the 1st TST is positive, consider the person infected • If the 1st TST is negative, administer 2nd TST in 1-3 weeks • If the 2nd TST is positive, consider the person infected • If the 2nd TST is negative, consider the person uninfected at baseline 25
  • 26. Infectiousness - 1 • Patients should be considered infectious if they: – Are undergoing cough-inducing procedures – Have sputum smears positive for acid-fast bacilli (AFB) and: • Are not receiving treatment • Have just started treatment, or • Have a poor clinical or bacterial response to treatment – Have cavitary disease • Extrapulmonary TB patients are not infectious 26
  • 27. Infectiousness - 2 • Patients are not considered infectious if they meet all these criteria: – Received adequate treatment for 2-3 weeks – Favorable clinical response to treatment – 3 consecutive negative sputum smears results from sputum collected on different days 27
  • 28. Techniques to Decrease TB Transmission • Instruct patient to: – Cover mouth when coughing or sneezing – Wear mask as instructed – Open windows to assure proper ventilation – Do not go to work or school until instructed by physician – Avoid public places – Limit visitors – Maintain home or hospital isolation as ordered 28
  • 29. Evaluation for TB • Medical history • Physical examination • Mantoux tuberculin skin test • Chest x-ray • Bacteriologic exam (smear and culture) 29
  • 30. Symptoms of TB • Productive prolonged cough* • Chest pain* • Hemoptysis* • Fever and chills • Night sweats • Fatigue • Loss of appetite • Weight loss *Commonly seen in cases of pulmonary TB 30
  • 31. Chest x-Ray • Obtain chest x-ray for patients with positive TST results or with symptoms suggestive of TB • Abnormal chest x-ray, by itself, cannot confirm the diagnosis of TB but can be used in conjunction with other diagnostic indicators 31
  • 32. Sputum Collection • Sputum specimens are essential to confirm TB – Specimens should be from lung secretions, not saliva • Collect 3 specimens on 3 different days • Spontaneous morning sputum more desirable than induced specimens • Collect sputum before treatment is initiated 32
  • 33. Smear Examination • Strongly consider TB in patients with smears containing acid-fast bacilli (AFB) • Use subsequent smear examinations to assess patient’s infectiousness and response to treatment 33
  • 34. Culture • Used to confirm diagnosis of TB • Culture all specimens, even if smear is negative • Initial drug isolate should be used to determine drug susceptibility 34
  • 35. Treatment of Latent TB Infection • Daily Isoniazid therapy for 9 months – Monitor patients for signs and symptoms of hepatitis and peripheral neuropathy • Alternate regimen – Rifampin for 4 months 35
  • 36. Treatment of TB Disease • Include four 1st-line drugs in initial regimen – Isoniazid (INH) – Rifampin (RIF) – Pyrazinamide (PZA) – Ethambutol (EMB) • Adjust regimen when drug susceptibility results become available or if patient has difficulty with any of the medications • Never add a single drug to a failing regimen • Promote adherence and ensure treatment completion 36
  • 37. Directly Observed Therapy (DOT) • Health care worker watches patient swallow each dose of medication • DOT is the best way to ensure adherence • Should be used with all intermittent regimens • Reduces relapse of TB disease and acquired drug resistance 37
  • 38. Clinical Monitoring Instruct patients taking TB medications to immediately report the following: – Rash – Nausea, loss of appetite, vomiting, abdominal pain – Persistently dark urine – Fatigue or weakness – Persistent numbness in hands or feet 38
  • 39. Drug Resistance • Primary - infection with a strain of M. tuberculosis that is already resistant to one or more drugs • Acquired - infection with a strain of M. tuberculosis that becomes drug resistant due to inappropriate or inadequate treatment 39
  • 40. Barriers to Adherence • Stigma • Extensive duration of treatment • Adverse reactions to medications • Concerns of toxicity • Lack of knowledge about TB and its treatment 40
  • 41. Improving Adherence • Adherence is the responsibility of the provider, not the patient and can be ensured by: – Patient education – Directly observed therapy (DOT) – Case management – Incentives/enablers 41
  • 42. Measures to Promote Adherence • Develop an individualized treatment plan for each patient • Provide culturally and linguistically appropriate care to patient • Educate patient about TB, medication dosage, and possible adverse reactions • Use incentives and enablers to address barriers • Facilitate access to health and social services 42
  • 43. Completion of Therapy • Based on total number of doses administered, not duration of treatment • Extend or re-start if there were frequent or prolonged interruptions 43
  • 44. Meeting the Challenge • Prevent TB by assessing risk factors • If risk is present, perform TST • If TST is positive, rule out active disease • If active disease is ruled out, initiate treatment for LTBI • If treatment is initiated, ensure completion 44
  • 45. Remember “A decision to test is a decision to treat.” 45